title: Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin.
abstract: Eukaryotic initiation factor eIF2B catalyses a key regulatory step in mRNA translation. eIF2B and total protein synthesis are acutely activated by insulin, and this requires phosphatidylinositol 3-kinase (PI 3-kinase). The epsilon-subunit of eIF2B is phosphorylated by glycogen synthase kinase-3 (GSK-3), which is inactivated by insulin in a PI 3-kinase-dependent manner. Here we identify the phosphorylation site in eIF2Bepsilon as Ser540 and show that treatment of eIF2B with GSK-3 inhibits its activity. Ser540 is phosphorylated in intact cells and undergoes dephosphorylation in response to insulin. This is blocked by PI 3-kinase inhibitors. Insulin-induced dephosphorylation of this inhibitory site in eIF2B seems likely to be important in the overall activation of translation by this hormone.
authors.affiliation: Department of Biosciences, University of Kent at Canterbury, UK.
authors.forename: G I
authors.initials: GI
authors.lastname: Welsh
authors.forename: C M
authors.initials: CM
authors.lastname: Miller
authors.forename: A J
authors.initials: AJ
authors.lastname: Loughlin
authors.forename: N T
authors.initials: NT
authors.lastname: Price
authors.forename: C G
authors.initials: CG
authors.lastname: Proud
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D017124:Conserved Sequence; D006224:Cricetinae; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011817:Rabbits; D012694:Serine / Q000378:metabolism*
chemical_list: D015852:Eukaryotic Initiation Factor-2; D007328:Insulin; D012694:Serine; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3